rs726788

Positions:

• chr19-14632433-A-G
• chr19-14632433-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032571.5(ADGRE3):​c.1643+488T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,014 control chromosomes in the GnomAD database, including 19,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19127 hom., cov: 31)
• Consequence: ADGRE3 NM_032571.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

ADGRE3 (HGNC:23647): (adhesion G protein-coupled receptor E3) This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 2 on chromosome 19. This protein may play a role in myeloid-myeloid interactions during immune and inflammatory responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

ADGRE3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE3	NM_032571.5	c.1643+488T>C		intron_variant		ENST00000253673.6	NP_115960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE3	ENST00000253673.6	c.1643+488T>C		intron_variant		1	NM_032571.5	ENSP00000253673.4
ADGRE3	ENST00000344373.8	c.1487+488T>C		intron_variant		1		ENSP00000340758.4
ADGRE3	ENST00000443157.6	c.1265+488T>C		intron_variant		2		ENSP00000396208.2
ADGRE3	ENST00000599900.5	c.998+488T>C		intron_variant		5		ENSP00000471853.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75482 AN: 151896 Hom.: 19117 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75526 AN: 152014 Hom.: 19127 Cov.: 31 AF XY: 0.491 AC XY: 36484 AN XY: 74278

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.501

Alfa AF: 0.516 Hom.: 41589

Bravo AF: 0.502

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs726788; hg19: chr19-14743245;